Protein Folding and Misfolding: A Perspective from Theory

The understanding of folding of proteins into their compact three-dimensional structures, example of complex biological self-assembly process, will provide an insight into the way in which evolutionary selection has influenced the properties of a molecular system for functional advantage. Once regarded as a grand challenge, protein folding has seen much progress in recent years. Protein folding pathways are of great interest not only in themselves, but also because understanding them is important for both protein structure predictions and for de novo protein design. Protein misfolding is a ubiquitous phenomenon associated with a wide range of diseases. Aggregation of misfolded proteins that escape the cellular quality-control mechanisms is a common feature of a wide range of highly debilitating and increasingly prevalent diseases. We hope that this review will stimulate further research in this area and catalyze increased collaboration at the interface of chemistry and biology to decipher the mechanisms and roles of protein folding, misfolding and aggregation in the fields of health and disease.